Investigation of the role of inositol and the phosphatidylinositol signal transduction system in mouse embryonic stem cells.

The aims of this study were to investigate in mouse embryonic stem cells (1) the requirement for myo-inositol for cell proliferation, (2) the incorporation of inositol into the phosphoinositides and inositol phosphates of the phosphatidylinositol (PtdIns) signal transduction system and (3) the effect of serum growth factors on PtdIns turnover. Exogenous myo-inositol was not essential for embryonic stem cell proliferation. Lithium, an inhibitor of endogenous inositol recycling, inhibited embryonic stem cell proliferation but this effect was not reversible by the addition of high concentrations of exogenous inositol. [3H]inositol was incorporated into the phosphoinositides, PtdIns, PtdIns4P and PtdIns(4,5)P2 in similar proportions as reported for other cells. [3H]inositol was also incorporated into a fourth lipid, tentatively identified as an inositolglycan. [3H]inositol was also incorporated into a number of inositol phosphates, with the greatest amount of incorporation after 24 h into an inositol pentakisphosphate. After serum starvation for 24 h, the addition of 10% whole or dialysed serum for 2 or 20 min increased (P < 0.05) incorporation into inositol tris- and tetrakisphosphates. These results demonstrate the presence of PtdIns system components in embryonic stem cells and increased PtdIns turnover in response to serum growth factors.